conflict of interest · 2018-02-22 · u.s. preventive task force 2016 in addition to the symptoms...

12/2/17

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“CardApnea:”CardiovascularDiseasesandSleepApnea

YeremYeghiazarians,MDProfessorofMedicine

InterventionalCardiologyLeone-PerkinsChairFamilyEndowedChairinCardiology

ImmediatePast-PresidentAmericanHeartAssociation,SFBoardUniversityofCalifornia,SanFrancisco

12/2/2017

ConflictofInterest

PastGuestSpeakerforApnea.Today

Today’sTopics

• BriefoverviewofOSA• OSAandcardiovascular(CV)diseases• OSAandCVoutcomes• TreatmentbenefitsofOSAonCVoutcomes• Costandsocietalimpact• WhichdoctorsdiagnosisOSA?• Guidelinerecommendations

WhatdoIknowasacardiologistaboutsleepapnea?

• Notenough• OfcourseIknowofthisconditionanditisonmy“radar”ofthings

thatIshouldbelookingfor,butit’snotlikemonitoringEKG,stresstest,cardiaccath,arrhythmia,echo,lipids,bloodpressure…..

• Whydon’tIdiagnosesleepapneamoreaggressivelyasacardiologist?– Ihavelotsofotherissuestoaddressduringalimitedofficevisit– Iamhopinganotherproviderwillhelpoutwiththis– Iwouldn’tknowwhattodoevenifapatientgotdiagnosedwithsleep

apnea– shortofreferringthemtoasleepspecialist!– IhavenoideahowtoadjustCPAPmachine– Ihavenoideawhen/ifsomeoneshouldgetCPAPoranoralappliance

orENTevaluation– IhavenoideahoweffectivetheCPAPororalapplianceisevenwhena

patientisbeingtreated– Iamjustnotcomfortable…..ButIknowIneedtodobetter

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Today’sTopics


ObstructiveSleepApnea(OSA)

• Disordercharacterizedbyrepetitiveepisodesofapnea

• Duetoupperairwayobstructionduringsleep• Cessationofbreathingforatleast10secondsisconsideredimportantandinmostpatients,apneiceventsare20-30secondsandsometimesevenlonger(~2-3minutes)!

• Sleepapneatypes:– Centralà neuraldrivetorespiratorymusclesisabolished

– Obstructiveà occlusionoftheoropharyngealairway

ObstructiveSleepApnea(OSA)– Cont’d

• OSAresultsinhemodynamic,autonomic,inflammatoryandmetaboliceffects:– Repetitiveepisodesofarousalleadtoactivationofneuro-hormonesandsympatheticnervoussystem,inflammatorycytokinerelease,anincreaseinreactiveoxygenspeciesandoxidativestress,endothelialdysfunctionandmetabolicdysregulation

• OSAcontributestonumerouscardiovasculardiseases

OSA– howisitdiagnosed?• History

– Snoring– Daytimesleepinessandtiredness– Drowsydriving– Nocturnalgaspingorchocking(witnessedapnea)– Restlesssleep– Poorconcentration– Morningheadaches– Irritability– Personalitychange

• PhysicalExam– Obesity,largeneckcircumference,hypertension,crowdedoropharyngealairway(largetongue,Mallampati scoreof3or4)

• SleepStudy

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OSADefinitions

U.S.PreventiveTaskForce2016

Inadditiontothesymptomsoutlined,thefollowingcanbeused(ifAHI≥15,regardlessofsymptoms,diagnosiscanbemade):

OvernightOximetryTesting

• Polysomnography istime-consumingandexpensive

• Manypatientsrefusetohavethistestdone• Homebasedtestingispreferabletomajorityofpatients

• ReliabilityisdependentonpretestprobabilityofOSA:– Inpatientswithhighestprobability,overnightoximetrycanconfirmthediagnosis

– Inpatientswithlowestprobability,itcanexcludediagnosis

OSAPrevalenceandRiskFactors

• Estimatedprevalenceis20-30%ofmalesand10-15%offemales(ifoneusesapnea-hypoxiaindex(AHI)of>5events/hourasmeasuredbypolysomnogram)

• AHI≥5events/hourwithsymptomsorAHI≥15events/hour- ~15%malesand~5%females

• Prevalenceisincreasingduetorisingratesofobesity

Epidemiology

Source:Primaryresearchwithexperts,U.S.Census(2014),Peppard"IncreasedPrevalenceofSleep-disorderedBreathinginAdults."AmericanJournalofEpidemiology(2013)

©AmericanAcademyofSleepMedicine2016

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Today’sTopics


OSAandCardiovascularDiseases• Hypertension• Atrialfibrillation• Otherarrhythmias• Suddencardiacdeath• Coronaryarterydisease• Heartfailure• Pulmonaryhypertension• Venousthromboembolism• Stroke• Endothelialdysfunction• Insulinresistance/Diabetes• Complicationswithmedicationsandsurgeries• Mortality

OSAandHypertension

• OSAandHTNfrequentlyexisttogetherinpatients• CohortandobservationalstudiesshowstrongassociationbetweenOSAandHTNandreportthatHTNprevalenceisincreasedinpatientswithOSA

• ThehigherAHI,thehigherthelikelihoodofHTN– AHI5-15à oddsratioofHTN2.0– AHI≥15à oddsratioofHTN2.9

• ResistantHTN(difficulttotreatrequiring3drugsatmaxdoses)isassociatedwithOSAin70-80%ofpatients

Peppard PEetalNEJM2000JanssenCetalJournalofHypertension2017MoonCetalClinicalNurseSpecialist2016

OSAandAtrialFibrillation

• StrongassociationbetweenOSAandAF(upto4-fold) – thisisindependentofotherfactors

• 50%ofpatientswithAFhavesleepapnea• UntreatedsleepapneaimpairstheabilitytocontrolAFib becauseitreducestheeffectivenessofcertainAFib treatments

• PatientswithsleepapneaarealsomorelikelytohaveAFib recurrencesafteracardioversionorcatheterablationcomparedtoAFibpatients

PatelNetalInternationalJournalofCardiology2017Mehra R– Obstructivesleepapneaandcardiovasculardisease2016

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OSAandotherArrhythmias• OSAappearstoincreasetheriskofnumerousothercardiacrhythmdisturbances,including:– Sicksinussyndrome– longpausesandbradycardia(reportedinupto~18%ofpatientswithsevereOSA)

– Bradycardiac-tachycardic events– Ventricularectopy andtachycardiamorecommon

• Non-sustainedVT5.3%vs.1.2% (severeOSAvscontrol)• Complexventricularectopy 25%vs.14%(severeOSAvs.control)

– Suddencardiacdeath• IncreasedriskifsevereOSA,desaturation<78%,age>60yearsold

PatelNetalInternationalJournalofCardiology2017Mehra RetalAm.J.Respir Crit CareMed2006Mehra R– Obstructivesleepapneaandcardiovasculardisease2016

OSAandUSSupremeCourtJusticeAntoninScalia

• ScaliaMayHaveForgottentoHookHimselfUptoSleepApneaMachine.WhyThatCanBeDangerous?

SleepReviewFebruary24,2016

• DidsleepapneacontributetoJusticeScalia’sdeath?Hisunpluggedbreathingmachineraisesthatquestion.

WashingtonPostFebruary24,2016

OSAandCoronaryArteryDisease• PatientswithsevereOSAappeartohaveanincreasedriskofdeveloping

CAD• ThehighertheAHI,thehighertheriskofCAD(Oddsratios3.1and8.7)• RiskofmajoradversecardiaceventsishigherinpatientswithOSAthan

without• ThereappearstobeanassociationofOSAwith:

– HTN– DecreasedHDL– IncreasedCRP(inflammatorymarker)– Increasedhomocysteine– Increasedglucoseandinsulinresistance– Increasedsympatheticactivity– Endothelialdysfunction– Hypoxia/hypercapnea– Elevatedhigh-sensitivitytroponin-Ilevels(withmoresevereOSAand

nocturnalhypoxia)àwhichmightresultinmyocardialinjury– OSAseverityassociationwithcoronarycalcification

Peker YetalEur Respir J1999MartinezDetalSleepBreath2011MoonCetalClinicalNurseSpecialist2016

OSAandHeartFailure(HF)• ThereisastrongrelationshipbetweenOSAandHF• PrevalenceofOSAinpatientswithHFishighandpatientswith

severeOSAare58%morelikelytodevelopHF(comparedtothosewithoutOSA)

• OSAisalsoassociatedwithnegativefunctionaloutcomesinpatientswithHF:– Increasedfluidretention– Reducedventricularfunction(OSAincreasesventriculartransmural

pressures;thereisincreasedafterloadanddecreasedpreload)– Alterationsinbloodgases– Increasedsympatheticactivity(knowntobedetrimentalin

cardiomyopathiesandleftventriculardysfunction)– Lowerexercisecapacity– Worsenedqualityoflife– Increasedmortality

MoonCetalClinicalNurseSpecialist2016Mehra R– Obstructivesleepapneaandcardiovasculardisease2016

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HeartFailureandSleepApnea

Javaheri S.etalJACC2017

ObservationalstudyofMedicarepatients,treatmentofOSAwasassociatedwithdecreasedreadmission,healthcarecostandmortality

OSAandPulmonaryHypertension(PH)

• PrevalenceofPHinpatientswithmoderate-severeOSAis~20%

• PrevalenceofnocturnalhypoxemiaandcentralsleepapneasarehighinPH(70–80%)sothesepatientsshouldallbescreenedforOSA

FeinDGetalJournalofClinicalMedicine2016ESC/ERSGuidelinesforthediagnosisandtreatmentofpulmonaryhypertension2015

OSAandVenousThromboembolism(VTE)

• OSAmightincreasetheriskofVTEby2-3fold• Likelypathophysiologicmechanisms:

– OSAresultsinendothelialdysfunction– Vasomotordysfunctionresultinginvasoconstriction(forexampleduetoincreasesinEndothelin andreactiveoxygenspeciesinOSA)

– Changesincelladhesiontotheluminalwall(ICAMandVCAMandanincreaseinmonocyteadhesiontotheendothelialwall)

– Increasesininflammatorycytokines(CRP,IL-6andTNF-α)– Hemostasisproblemssuchasincreasedplateletactivityandhyperaggregability state(forexampleD-DimerandTissueFactor)inOSA

Deflandre EetalObes Surg 2016Mehra R– Obstructivesleepapneaandcardiovasculardisease2016

OSAandStroke• PatientswithOSAhaveahigherriskofstroke• UntreatedOSAisanindependentmodifiableriskfactorforstroke

• Arecentmeta-analysiscalculatedthatsevereOSAisassociatedwithanincreasedriskofstrokeof~2.1fold

• Possiblemechanisms:– Increasedriskofarrhythmias,especiallyAtrialFibrillation– Hypercoagulable state– Right-to-leftshunting(viaapatentforamenovale)inpatientswithpulmonaryHTNandOSA

– Hypoxia/Hypercapnea andincreasedsympathetictone– IncreasedriskofHTNinpatientswithOSA

ChengSetalPract Neurol 2016MoonCetalClinicalNurseSpecialist2016Mehra R– Obstructivesleepapneaandcardiovasculardisease2016

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OSAandInsulinResistance/Diabetes• PatientswithOSAhaveanincreasedprevalenceofinsulin

resistanceanddiabetes• Obesityinthesepatientsiscontributingbutthereappearstobean

independentassociationbetweenOSAseverityandinsulinresistance/diabetes

• PatientswithsevereOSAhavea30%higherriskofdiabetescomparedtopatientswithoutOSA

• Possiblemechanisms:– Intermittenthypoxiamightimpairinsulinsensitivity– Highsympatheticneuralactivityincreasesthelevelsofplasma

catecholamines anddecreasesinsulinsensitivity– Sleepapneacouldincreasethehypothalamopituitary-adrenalaxis

activity,thelevelofplasmacortisolandinsulinresistance– Elevatedlevelsofmarkersofinflammation– Increasedlevelsofglucoseandtriglycerides

LouisMetalJAppliedPhysiol 2009LiuCLetalCanadianJournalofDiabetes2016MoonCetalClinicalNurseSpecialist2016Mehra R– Obstructivesleepapneaandcardiovasculardisease2016

OSAandComplicationswithMedicationsandSurgeries

• OSAsignificantlyincreasesriskofsomemedicationsandsurgeries• Anesthesia/sedativescanmaketheconditionworse• PatientswithOSAareatriskofdevelopingrespiratoryand

cardiopulmonarycomplicationspostoperatively• Surgeonsofallspecialties,andespeciallyanaesthetists,shouldbe

awarethatundiagnosedOSAiscommon• Consider:

– alternativemethodsofpainrelief– useofnasalcontinuousairwaypressurebeforeandaftersurgery– surveillanceinanintensivecareunit,especiallyafternasalsurgeryinwhichpacksareused

– andrememberthatsomeofthesepatientscangetintotroubleacoupleofdaysafterthesurgery!

HerderCDetalBMJ2004

Today’sTopics


OSAandAll-CauseMortality


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OSAandCVMortality


Today’sTopics


OSATherapyandCVoutcomes

• Threecategories:– Behavioral– Medical(Non-surgical)– Surgical

OSATherapyandCVoutcomes• Threecategories:

– Behavioral• Avoidfactorsthatincreaseriskofupperairwayclosure:

– Alcohol– Sedatives/Hypnoticagents– Weight– Smoking

– Medical(Non-surgical)• Positiveairwaypressure+/- humidifier• Oxygensupplementation• Dental/Oralappliances

– Surgical– someoptions:• Tracheostomy• Jawrepositioning• Implants• Palatalsurgery(Uvulopalatopharyngoplasty)– curativein<50%patients

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OralAppliances(OA)• Twomaincategories:

– Devicesthatholdthetongueforward– Devicesthatrepositionthejaw(adjustableandbettertolerateddevicesare

beingused)• AmericanAcademyofSleepMedicinerecommendation:

– OAasfirstlinetherapyformildandmoderateOSA– OAforsevereOSApatientsintolerantofCPAP

• Data:– OAsdecreasesleepiness– OAsdecreasesnoring– OAsimprovequalityoflifeandneuropsychologicalfunction– IntermsofreducingAHI,CPAPappearstobemoreeffectivethatOA(especially

inpatientswithsevereOSA)– 2013observationalstudy- bothCPAPandOAmaybeequallyeffectivetherapy

inreducingtheriskoffatalcardiovascularevents(MI,stroke,arrhythmicdeaths)inpatientswithsevereOSA

• Compliance - ~6.8hours/night• Longterm compliance– variablereports:anywherefrom70-80%at12monthsvs.

45-80%at3-4years

AlmeidaFRandLoweAA2009;Anandam Aetal2013;FergusonKAetal2006

CPAP- OSATherapyandCVoutcomes

• CPAPreducesbloodpressureby~3mmHg– long-termreductionsof2-3mmHginSBPareassociatedwitha4%to8%reductioninthefutureriskofstrokeandheartdisease

• CPAPreducesbloodpressureevenmoreinresistantHTN(between4.7-7.2mmHgand2.9-4.9mmHgforSBPandDBP,respectively)

• Inasmallrandomizedcrossoverstudy(therapeuticvs.shamCPAP),12weeksofCPAPtreatmentresultedinasignificantdecreaseinpulmonaryarterysystolicpressureandthisreductionwasgreatest(8.5mmHg)inpatientswithbaselinePHTN(pulmonaryarterysystolicpressure~30mmHg)

• CPAPtreatmentisassociatedwithdecreasedrecurrencerateofAF,evenafterelectricalcardioversionorablativetherapies

Javaheri S.etalJACC2017

OAvs.CPAPeffectiveness

SutherlandKetal;2015 NEJM2016

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SAVETrial• AIM

– TodetermineifCPAPtreatmentofmoderatetosevereOSAinpatientswithCVdiseasewouldreducetheincidenceoffutureCVevents

• STUDYDESIGN– Multinational,open-labelRandomizedControlledTrial– CPAP+UsualCarevs. UsualCarealone– Primaryendpoint:compositeofcardiovasculardeath,MI,

stroke,hospitalizationforTIA,unstableanginaorHF– Secondaryendpoints:OtherCVoutcomes,health-relatedqualityof

life,snoringsymptoms,daytimesleepiness,andmood

• 2717pts;followedforaverageof3.7years

NEJM2016

SAVETrial– inclusion/exclusioncriteria

• Ages45-75yearsoldwithmoderate-severeOSAwhocoulduseCPAPmask>3hours/night

• Historyofcoronaryorcerebrovasculardisease• Excluded:

– Severesleepiness/riskoffallasleepaccident– Verysevereoxygendeprivation– Advancedheartfailure– PriorCPAPuse– Centralsleepapnea

SAVETrial– Summary

• NoeffectofCPAPtreatmentonPrimaryCVendpoints

• TrendtowardreductionincerebrovasculareventsinpatientswhousedCPAP>4hourspernight

• CPAPimproved:– Patientwell-being– Lesssnoring– Lessdaytimesleepiness– Lessdepressedfeelings– ImprovedQoL– Fewerworkdayslostduetoill-health

NEJM2016

LimitationsoftheSAVETrial• ManypatientswithpriorCPAPuseandseverehypoxemiawereexcludedfromthestudy

• CPAPadherencewasonly3.3hours/night!• Thisisprobablylessthanhalfthetimethepatientsweresleeping

• Anongoingtrial,ISAACCStudyisbeingperformedtoassesstheeffectofCPAPinnonsleepy patientswithOSAandacutecoronarysyndromes

à NeedforbetterCPAPadherenceorbetterdevicesisCRUCIAL!

Mokhlesi BandAyas NTNEJM2016

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Today’sTopics


CostandSocietalImpactofOSA


Today’sTopics


Ascardiologistswedoverypoorly!


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OSA Treatment Whattreatmentdidyoubeginupondiagnosisof

sleepapnea?(n=506)

Inanaveragenight,forhowmanyhoursofsleepdoyouwearyourCPAP/OralAppliance.Forhowmanyyearshaveyoubeenusingthefollowingtreatments?

92%

6% 3% 3% 6% 7% 2%

CPAP (or PAP/AutoPAP/BiPAP) Oral Appliances Surgery (within the year)Surgery for weight loss (within the year) Non-Surgical Weight Loss Change for sleep positioningOther None


Today’sTopics


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Summary• OSAsignificantlyincreasesriskofnumerouscardiovasculardiseasesand

leadstoworseoutcomes• Earlyidentificationandscreeningisessential• Initiationofearlytherapyiscritical• CompliancewithCPAPispoorandnovelmethodsoftherapyaremuch

needed• Mild-moderatesleepapnea– consideroralappliancewhichmightbe

bettertolerated• Severeapnea– inmyopinion,patientsshouldbescreenedbyENTto

ruleoutobstructiveissuespriortostartingCPAP• Onceatherapyisinitiated,follow-upsleepscreeningshouldbe

performed– atleastyearly• CostandimpactofOSAisveryhigh• Multi-disciplinaryteamapproach(includingcardiologists,dentists,ENT,

pulmonologistsandsleepspecialists)aregoingtoplayanincreasinglycrucialroleinthediagnosisandmanagementofpatientswithOSA

THANKYOU

conflict of interest · 2018-02-22 · u.s. preventive task force 2016 in addition to the symptoms...

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